![]() ![]() For instance, polySia is present on activated dendritic cells, where it has been described as a regulator of cell trafficking. Besides being involved in the plasticity of the nervous system and the development of several organs, polySia plays also a role in immunological processes. Two polysialyltransferases can modify distinct proteins, e.g., the neural cell adhesion molecule (NCAM), with this posttranslational modification. Polysialic acid (polySia) is a negatively charged carbohydrate consisting of α2,8-linked N-acetylneuraminic acid residues in mammalians. Thus, polySia is a physiological element in plasma and may represent a natural buffer for extracellular histones. ![]() Intriguingly, polySia is not only present in human plasma but also in fish and other branches of vertebrates. Chain length analysis revealed that polySia chains originating from human plasma can consists of more than 40 sialic acid residues and show a cytoprotective effect against extracellular histones. Remarkably, we detected polySia not only in the soluble fraction of plasma, but also on enriched extracellular vesicles (EVs). In the present study, we examined the chain length of polySia in plasma and tested its ability to decrease the cytotoxic characteristics of extracellular histones. Interestingly, the carbohydrate polysialic acid (polySia) can bind histones and reduce histone-mediated cytotoxicity in a chain length-dependent manner. ![]() Several researchers have demonstrated that the cytotoxic characteristics of these histones can trigger diseases like sepsis. During this process, high concentrations of extracellular histones can be reached. By spreading out chromatin, antimicrobial peptides and enzymes, neutrophils efficiently trap pathogens like bacteria and facilitate their elimination. The innate immune system has numerous mechanisms to fight against pathogens, including the formation of neutrophil extracellular traps (NETs). ![]()
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